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Lege Artis Medicinae

JUNE 20, 2005

[THE CLINICAL PHARMACOLOGIC BASIS OF THE SAFE USE OF STATIN ANALOGS]

KERPEL-FRONIUS Sándor

[Statins, specific inhibitors of the 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA), decrease significantly pathologically elevated cholesterol levels. The effectiveness and the side effects of the different analogs depend on their inhibitory potency, lipid solubility, active uptake into the liver cells and on the difference in their metabolism. The statins can be divided into three groups on the basis of their clinical effectiveness: the highly effective agents are rosuvastatin and atorvastatin; simvastatin exhibits an intermediate activity, while lovastatin, pravastatin and fluvastatin are the least active drugs. The main metabolic pathways of the statins are oxidation and glucoronidation and finally the spontaneous inactivation by lactone ring formation of the glucoronidated products. Gemfibrozil increases the plasma level of all statin analogs by inhibiting the activity of UGT1A1 and UGT1A3 isoenzymes of the UDPglucoronosyltransferase. Therefore, when a statinfibrate combination is needed, fenofibrate and bezafibrate are recommended, the metabolism of which are linked to other UGT isoenzymes. Similarly elevated plasma levels are produced by inhibiting the specific cytochrome isoforms participating in the oxidation of a particular statin. Severe side effects are rarely observed. The most frequent adverse reaction is the development of myopathy of various severity. Using various statins rhabdomyolysis occurred in 0.0-0.3 cases /100 000 statin prescriptions if the already withdrawn cerivastatin is not considered. The statin+gemfibrozil combination increases the number of rhabdomyolysis approximately tenfold. The long-term benefit of statin therapy far exceeds the risk of the treatment. For achieving very low lipid target values even the most effective statins must be used in high doses. Nevertheless, this goal cannot be reached in about 20% of the cases. High dose statin treatment should be administered with the gradual increase of the dose, tight control of the patients and by meticulously selecting the drugs given simultaneously. Further development can be expected from the application of agents with new mechanisms of action, such as the cholesterol uptake inhibitor ezetimibe.]

Lege Artis Medicinae

JUNE 20, 2011

[A new approach to the treatment of diabetic retinopathy - PPAR-α agonist activity of fenofibrate]

CSÁSZÁR Albert

[Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. It affects nearly half of patients with diabetes and its severity increases with the progress of diabetes. Glycotoxicity, lipotoxicity and hypertension are the main risk factors for the development of DR. The control of glucose homeostasis and blood pressure are the main noninvasive approaches that might have a role in the treatment of this condition. On the basis of new studies, RAS inhibitors and fenofibrate are promising candidates that can be used to retard DR progression and/or induce its regression. Two large-scale studies (FIELD, ACCORD Eye) have demonstrated that fenofibrate therapy significantly reduces the need for laser treatment of DR. The efficiency of this therapy, which is independent of lipid changes, is primarily attributable to the PPAR-α agonist activity of fenofibrates. According to guidelines that discuss the new therapeutic approaches of DR, fibrate therapy is a promising new option for preventing the progression of DR.]